Rega Institute for Medical Research, Minderbroedersstraat 10, KU Leuven, B-3000 Leuven, Belgium.
Curr Opin Virol. 2011 Dec;1(6):590-8. doi: 10.1016/j.coviro.2011.10.030. Epub 2011 Nov 29.
Roughly 20 years after the discovery of the hepatitis C virus (HCV), and 10 years after the launch of the current standard of care (SOC) therapy, i.e. the combination of pegylated interferon-alpha and ribavirin, antiviral treatment of chronic hepatitis C is at the dawn of a new era. The current SOC will be combined with a direct acting antiviral (DAA), i.e. either the HCV NS3 protease inhibitor Telaprevir or Boceprevir. Combinations of DAAs may have the potential to completely cure chronic HCV infection. Clinical data suggest that ribavirin may remain at least for some time, an important component even in combinations of different DAAs. Ironically, and much in contrast to the DAAs, the precise mechanism(s) by which ribavirin exerts its anti-HCV activity in infected patients still waits to be unravelled. Here we review the current views on the mechanism of action of ribavirin against chronic infections with HCV. Concerted efforts of modern pharmacogenetics, novel insights into innate immunity and contributions from molecular virology will hopefully allow deciphering the precise mechanism(s) that are at the basis of the antiviral effect of this nucleoside analogue. Such insights may help design improved strategies to fight chronic infections with HCV.
在发现丙型肝炎病毒（HCV）大约 20 年后，在推出目前的标准治疗（SOC）疗法 10 年后，即聚乙二醇干扰素-α和利巴韦林联合治疗，慢性丙型肝炎的抗病毒治疗正处于一个新时代的黎明。目前的 SOC 将与直接作用抗病毒药物（DAA）联合使用，即 HCV NS3 蛋白酶抑制剂特拉匹韦或博赛匹韦。DAA 的联合使用有可能彻底治愈慢性 HCV 感染。临床数据表明，利巴韦林至少在一段时间内，即使在不同 DAA 的联合治疗中，仍可能是一个重要组成部分。具有讽刺意味的是，与 DAA 形成鲜明对比的是，利巴韦林在感染患者中发挥抗 HCV 活性的确切机制仍有待揭示。在这里，我们回顾了利巴韦林针对慢性 HCV 感染的作用机制的最新观点。现代药物遗传学的协同努力、先天免疫的新见解以及分子病毒学的贡献，有望阐明这种核苷类似物抗病毒作用的精确机制。这些见解可能有助于设计改善策略来对抗慢性 HCV 感染。
